Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT99QR7R)

• DOT Name: Mitochondrial import inner membrane translocase subunit Tim10 (TIMM10)
• Gene Name: TIMM10
• Related Disease:
  African trypanosomiasis
  Lung adenocarcinoma
  Rhabdomyosarcoma
• UniProt ID: TIM10_HUMAN
• PDB ID: 2BSK; 7CGP
• Pfam ID: PF02953
• Sequence:
  MDPLRAQQLAAELEVEMMADMYNRMTSACHRKCVPPHYKEAELSKGESVCLDRCVSKYLD
  IHERMGKKLTELSMQDEELMKRVQQSSGPA
• Function: Mitochondrial intermembrane chaperone that participates in the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. May also be required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space.
• Tissue Specificity: Ubiquitous, with highest expression in heart, kidney, liver and skeletal muscle.
• Reactome Pathway: Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
African trypanosomiasis	DISBIXK4	Strong	Genetic Variation	[1]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[2]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[3]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Mitochondrial import inner membrane translocase subunit Tim10 (TIMM10).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial import inner membrane translocase subunit Tim10 (TIMM10).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial import inner membrane translocase subunit Tim10 (TIMM10).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Mitochondrial import inner membrane translocase subunit Tim10 (TIMM10).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Mitochondrial import inner membrane translocase subunit Tim10 (TIMM10).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Mitochondrial import inner membrane translocase subunit Tim10 (TIMM10).	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mitochondrial import inner membrane translocase subunit Tim10 (TIMM10).	[7]

References

• [1] Divergent Small Tim Homologues Are Associated with TbTim17 and Critical for the Biogenesis of TbTim17 Protein Complexes in Trypanosoma brucei.mSphere. 2018 Jun 20;3(3):e00204-18. doi: 10.1128/mSphere.00204-18. Print 2018 Jun 27.
• [2] c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
• [3] Identification of novel genes expressed during rhabdomyosarcoma differentiation using cDNA microarrays.Pathol Int. 2006 May;56(5):246-55. doi: 10.1111/j.1440-1827.2006.01958.x.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [10] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.